The theme of this proposed Botanical Dietary Supplement Research Center (BDSRC) are to define the molecular and cellular mechanisms by which bioactive botanicals may beneficially promote psychological resilience in the context of social defeat (Project 1), preserve cognitive function in the context of sleep deprivation (Project 2), and to develop probiotic supplements that can optimize the utilization of these specific botanicals (Project 3), with the final goal to develop bioactive botanicals with defined mechanisms of action for immediate application in humans. Critical to this goal are objective measures of the biological effects of the botanical supplements on brain function in the context of chronic social defeat and sleep deprivation. Core C will support the overall goals of the BDSRC by facilitating preclinical behavioral testing and electrophysiology analysis. The Behavioral Phenotyping Component will use multiple behavioral measures to determine how botanical supplements affect behavioral functioning. Following an initial assessment designed to exclude any significant motor or sensory deficits that would confound interpretation of more complex tests, chronic social defeat stress and social avoidance (social interaction) test will be performed for Project 1. For Project 2, a series of behavioral tests will be administered that will emphasize the core behavioral features of memory dysfunction. Testing will include assays to detect anxiety related behavior as well as tests designed to measure learning and memory related functions, including the Morris water maze, contextual and cued fear conditioning, a Y-maze working memory task, and a novel object recognition task. The Electrophysiology Component will measure excitatory and inhibitory synaptic plasticity in the nucleus accumbens (NAc) to dissect the mechanistic role of phenolic metabolites on promotion of resilience to chronic social stress (Research Project 1). The Electrophysiology Component will also measure synaptic plasticity in the hippocampal formation to assess the role of phenolic metabolites on cognitive function in the context of acute and chronic sleep deprivation (Research Project 2). Collectively Core C will support the goals of individual projects by providing objective measures that will allow the biological effects of botanical supplements to be correlated with synaptic activity and function. Core C will also provide toxicology analysis for safety profiles for preclinical in vivo studies.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Specialized Center (P50)
Project #
5P50AT008661-03
Application #
9312230
Study Section
Special Emphasis Panel (ZAT1)
Project Start
Project End
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Jiang, C; Lin, W-J; Sadahiro, M et al. (2018) VGF function in depression and antidepressant efficacy. Mol Psychiatry 23:1632-1642
Smith, Chad; Frolinger, Tal; Brathwaite, Justin et al. (2018) Dietary polyphenols enhance optogenetic recall of fear memory in hippocampal dentate gyrus granule neuron subpopulations. Commun Biol 1:42
Ho, Lap; Ono, Kenjiro; Tsuji, Mayumi et al. (2018) Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms. Expert Rev Neurother 18:83-90
Blaze, Jennifer; Wang, Jun; Ho, Lap et al. (2018) Polyphenolic Compounds Alter Stress-Induced Patterns of Global DNA Methylation in Brain and Blood. Mol Nutr Food Res 62:e1700722
Pfau, Madeline L; Ménard, Caroline; Russo, Scott J (2018) Inflammatory Mediators in Mood Disorders: Therapeutic Opportunities. Annu Rev Pharmacol Toxicol 58:411-428
Aleyasin, Hossein; Flanigan, Meghan E; Golden, Sam A et al. (2018) Cell-Type-Specific Role of ?FosB in Nucleus Accumbens In Modulating Intermale Aggression. J Neurosci 38:5913-5924
Aleyasin, Hossein; Flanigan, Meghan E; Russo, Scott J (2018) Neurocircuitry of aggression and aggression seeking behavior: nose poking into brain circuitry controlling aggression. Curr Opin Neurobiol 49:184-191
Ho, Lap; Cheng, Haoxiang; Wang, Jun et al. (2018) A Comprehensive Database and Analysis Framework To Incorporate Multiscale Data Types and Enable Integrated Analysis of Bioactive Polyphenols. Mol Pharm 15:840-850
Takahashi, Aki; Flanigan, Meghan E; McEwen, Bruce S et al. (2018) Aggression, Social Stress, and the Immune System in Humans and Animal Models. Front Behav Neurosci 12:56
Ho, Lap; Zhao, Danyue; Ono, Kenjiro et al. (2018) Heterogeneity in gut microbiota drive polyphenol metabolism that influences ?-synuclein misfolding and toxicity. J Nutr Biochem 64:170-181

Showing the most recent 10 out of 36 publications